title: SOCS1 and SOCS3 are the main negative modulators of the somatotrophic axis in liver of homozygous GH-transgenic zebrafish (Danio rerio).
abstract: Homozygote individuals (HO) of the GH-transgenic zebrafish lineage (F0104), despite expressing double the amount of growth hormone (GH) in relation to the hemizygote (HE) individuals, presented smaller growth in relation to the last, and similar to the non-transgenic (NT) group. Through the analysis of the expression of genes of the somatotrophic axis in the livers of HO and NT individuals, it was verified that GHR, JAK2 and STAT5.1 did not present significant differences among the analyzed genotypes (NT and HO). However, in the IGF-I gene expression, an accentuated decrease was observed in group HO (p<0.01), suggesting a resistance effect to excess GH. This resistance could be related to the insufficient amount of energy for supporting the accelerated metabolic demand caused by excess circulating GH. Analysis of the genes involved in the regulation of GH signalization by dephosphorylation (PTP-H1 and PTP-1B) did not show any significant alteration when comparing groups HO and NT. However, the analysis of the SOCS1 and SOCS3 genes showed an induction in homozygotes of 2.5 times (p<0.01) and 4.3 times (p<0.05), respectively, in relation to non-transgenics. The results of the present work demonstrate that, in homozygotes, GH signaling is reduced by the action of the SOCS1 and SOCS3 proteins.
authors.affiliation: Programa de Pós-Graduação em Ciências Fisiológicas: Fisiologia Animal Comparada, Universidade Federal do Rio Grande-FURG, Rio Grande, RS, Brazil.
authors.forename: Ana Lupe Motta
authors.initials: AL
authors.lastname: Studzinski
authors.forename: Daniela Volcan
authors.initials: DV
authors.lastname: Almeida
authors.forename: Carlos Frederico Ceccon
authors.initials: CF
authors.lastname: Lanes
authors.forename: Márcio de Azevedo
authors.initials: Mde A
authors.lastname: Figueiredo
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Marins
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D013006:Growth Hormone / Q000502:physiology*; D006720:Homozygote; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D029961:Zebrafish Proteins; C494098:ihb394 protein, zebrafish; C540939:socs1a protein, zebrafish; C540940:socs3a protein, zebrafish; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D053614:Janus Kinase 2